The crash happened in the eastbound lanes of the highway in the Grays Ferry section.
Police say the 41-year-old victim lost control of his bike around 3 a.m. He was tossed into the roadway and hit by a car.
The man's name has not been released.
The lanes were closed for more than five hours, finally reopening around 9 a.m.
The eastbound Schuylkill Expressway has reopened after being shut down for five and a half hours following a fatal motorcycle crash in Grays Ferry.
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